The dendrites of the hippocampal pyramidal cells generate action potentials. The proposed experiments will use electrophysiological techniques to investigate fundamental questions concerning dendritic excitability. Using the in vitro hippocampal slice preparation, we have obtained intracellular recordings from the apical dendrites of the pyramidal cells and demonstrated and oscillating bursts of action potentials can be generated independently in the dendrites. The principal objective of this program is to contribute to our understanding of the intrinsic and extrinsic factors controlling the dendritic excitability. The immediate objectives are (1) to test the Ca++-dependency of three membrane events important in the generation of bursts. These events are the spike depolarizing and hyperpolarizing after potentials and the TTX resistant spikes; (2) to examine the effect of norepinephrine and serotonin or dendritic excitability and (3) to characterize the inhibitory process that regulates dendritic excitability during synaptic activation. The in vitro slice preparation will be used in all of the experiments. This preparation provides mechanical stability and enables precise control of ionic composition of the perfusion medium as well as drug concentration. More importantly, the direct intradendritic recording technique has been developed using this preparation. This technique, together with an intracellular dye injection procedure, will allow us to study dendritic excitability and its regulation in a more direct manner that has ever been possible before. Our initial studies using this approach have already provided new information concerning the differential membrane properties of the dendrites and somata of the pyramidal cells. The possible differential control of these two regions by synaptic mechanisms remains to be elucidated. These initial studies have also directly demonstrated the role of normal dendritic activities in the production of the intense neuronal discharge during penicillin-induced epiliptiform activities.